Amino acid compounds

ABSTRACT

Carnitine and Taurine Compounds are described. The Carnitine Compound comprises Carnitine and one of a Nitrate and a Nitrite. The Taurine Compound comprises Taurine and one of a Nitrate and a Nitrite.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part application of the earlierU.S. Utility patent application to Ronald Kramer, et. al. entitled“Amino Acid Compounds,” application Ser. No. 11/950,273, filed Dec. 4,2007, now pending, which application claims the benefit of the filingdate of U.S. Provisional Patent Application 60/973,229 entitled “AminoAcid Compounds” to Alexander Nikolaidis and Ronald Kramer which wasfiled on Sep. 18, 2007, the disclosures of which is hereby incorporatedentirely herein by reference.

BACKGROUND

1. Technical Field

Aspects of this document relate generally to Taurine and CarnitineCompounds.

2. Background

It is desirable to design new Taurine and Carnitine compounds that haveproperties lacking in conventional Taurine and Carnitine compounds,conventional Nitrate compounds, conventional Nitrite compounds, and insingle-administration Taurine and Carnitine products.

SUMMARY

In one aspect, this document features a carnitine compound comprisingCarnitine and one of a Nitrate and a Nitrite.

Particular embodiments may include one or more of the following. TheCarnitine compound may further comprise a pharmaceutically acceptableadditive, wherein the additive is one of a carrier, excipient, binder,colorant, flavoring agent, preservative, buffer, dilutant, andcombinations thereof. The Carnitine compound may be in the form of acapsule, tablet, pill, liquid, liquid suspension, vapor, gas, powder,granulate or pulverulence.

In another aspect, this document features a carnitine compoundcomprising Taurine and one of a Nitrate and a Nitrite.

Particular embodiments may include one or more of the following. TheTaurine compound may further comprise a pharmaceutically acceptableadditive, wherein the additive is one of a carrier, excipient, binder,colorant, flavoring agent, preservative, buffer, dilutant, andcombinations thereof. The Taurine compound may be in the form of acapsule, tablet, pill, liquid, liquid suspension, vapor, gas, powder,granulate or pulverulence.

In yet another aspect, this document features a method for increasingwater solubility of one of Carnitine and Taurine in a human or animal,which comprises administering a pharmaceutically effective amount of oneof a Carnitine Compound comprising Carnitine and one of a Nitrate and aNitrite and a Taurine Compound comprising Taurine and one of a Nitrateand a Nitrite to the human or animal.

Particular embodiments may include one or more of the following.Increasing water solubility may further comprise increasing thebioabsorption of one of Carnitine and Taurine in a human or animal.Increasing water solubility may further comprise increasing thevasodilative characteristics of one of Carnitine and Taurine in a humanor animal.

In still another aspect, this document features a method for preventingthe development of nitrate tolerances in a human or animal, whichcomprises administering a pharmaceutically effective amount of one of aCarnitine Compound comprising Carnitine and one of a Nitrate and aNitrite and a Taurine Compound comprising Taurine and one of a Nitrateand a Nitrite to the human or animal.

The foregoing and other aspects, features, and advantages will beapparent to those of ordinary skill in the art from the DESCRIPTION andfrom the CLAIMS.

DESCRIPTION

Overview

Compounds containing both a carboxyl group and an amino group aretypically known as Amino Acids. Amino Acids typically have the basicformula X—R, wherein X is:

Amino Acids typically differ from one another with respect to thestructure of the R group. It is the structure of the R group thattypically determines the individuality and character of each Amino Acid.

In addition, many Amino Acid derivatives and products of Amino Acidbiosynthesis themselves may have biological and physiological effects.

For example, Carnitine is a quaternary ammonium compound biosynthesizedfrom the amino acids lysine and methionine. Acetyl-L-Carnitine is analternative form of carnitine with an acetyl group coupled with thehydroxyl group of the third carbon molecule. Propionyl-L-carnitine isanother alternative form of carnitine that contains a propionyl groupcoupled with the third carbon molecule. The chemical structures ofCarnitine, Acetyl-L-Carnitine, and Propionyl-L-carnitine are as follows:

Significantly, neither carnitine nor its alternative forms possessvasodilating properties. In addition, since carnitine and itsalternative forms are bipolar molecules, their solubility might belowered with respect to pH. Carnitine is presently used in the dietarysupplement industry to supplement Carnitine production in the body.Carnitine is also presently used in the dietary supplement industry toimprove athletic performance, enhance mood, and boost immune response.Various supplemental Carnitine forms are available in the consumermarketplace.

In addition to the foregoing example, Taurine is a derivative of thesulfur-containing amino acid Cysteine. Taurine by itself has novasodilating properties. Taurine is presently used in the dietarysupplement industry to supplement Taurine production in the body.Taurine is also presently used in the dietary supplement industry toimprove athletic performance and resist muscle cramps. Varioussupplemental Taurine forms are available in the consumer marketplace,including many sports supplements and energy drinks.

Nitrates are a class of compounds that are salts of Nitric Acid (HNO₃)and at least comprise one Nitrogen atoms and three Oxygen atoms (NO₃).In addition, Nitrites are a class of compounds that are salts of NitrousAcid (HNO₂) and at least comprise one Nitrogen atom and two Oxygen atoms(NO₂).

Nitrates and Nitrites are commercially available in various preparationsand are used in various commercial applications. In the case ofingestion by humans, Nitrate (NO₃) is typically reduced to Nitrite (NO₂)in the epithelial cells of blood vessels. In vivo, Nitrite (NO₂) reactswith a thiol donor, principally glutathione, to yield Nitric Oxide (NO).

TERMINOLOGY AND DEFINITIONS

In describing implementations of an Amino Acid Compound, the followingterminology will be used in accordance with the definitions andexplanations set out below. Notwithstanding, other terminology,definitions, and explanations may be found throughout this document, aswell.

As used herein, “Amino Acid” is a term used in its broadest sense andmay refer to an Amino Acid in its many different chemical formsincluding a single administration Amino Acid, its physiologically activesalts or esters, its combinations with its various salts, itstautomeric, polymeric and/or isomeric forms, its analog forms, itsderivative forms, its biosynthesis products and/or its decarboxylationproducts. Amino Acids comprise, by way of non-limiting example:Agmatine, Beta Alanine, Arginine, Asparagine, Aspartic Acid, Cysteine,Glutamine, Glutamic Acid, Glycine, Histidine, Isoleucine, Leucine,Lysine, Methionine, PhenylBeta Alanine, Proline, Serine, Threonine,Tryptophan, Tyrosine, and Valine.

As used herein, “Compound” is a term used in its broadest sense and mayrefer to an Amino Acid in combination with one of a Nitrate and aNitrite.

As used herein, “Nitrate” is a term used in its broadest sense and mayrefer to an Nitrate in its many different chemical forms including asalt of Nitric Acid, a single administration Nitrate, itsphysiologically active salts or esters, its combinations with itsvarious salts, its tautomeric, polymeric and/or isomeric forms, itsanalog forms, and/or its derivative forms. Nitrate comprises, by way ofnon-limiting example, many different chemical forms including dinitrateand trinitrate. Nitrates may be salts, or mixed salts, of Nitric Acidand comprise one Nitrogen atom and three Oxygen atoms. For the exemplarypurposes of this disclosure, Nitrate may comprise salts of Nitrate suchas sodium nitrate, potassium nitrate, barium nitrate, calcium nitrate,and the like. For the exemplary purposes of this disclosure, Nitrate mayinclude mixed salts of Nitrate such as nitrate orotate, and the like.Additionally, for the exemplary purposes of this disclosure, Nitrate maycomprise nitrate esters such as nitroglycerine, and the like.

As used herein, “Nitrite” is a term used in its broadest sense and mayrefer to an Nitrite in its many different chemical forms including asalt of Nitrous Acid, a single administration Nitrite, itsphysiologically active salts or esters, its combinations with itsvarious salts, its tautomeric, polymeric and/or isomeric forms, itsanalog forms, and its derivative forms. Nitrite comprises, by way ofnon-limiting example, many different chemical forms including dinitriteand trinitrite. Nitrites may be salts, or mixed salts, of Nitrous Acidand comprise one Nitrogen atom and two Oxygen atoms. For the exemplarypurposes of this disclosure, Nitrite may comprise salts of Nitrite suchas sodium nitrite, potassium nitrite, barium nitrite, calcium nitrite,and the like. For the exemplary purposes of this disclosure, Nitrite maycomprise mixed salts of Nitrite such as nitrite orotate, and the like.Additionally, for the exemplary purposes of this disclosure, Nitrite maycomprise nitrite esters such as amyl nitrite, and the like.

As used herein, “pharmaceutically acceptable additive” or “additive” areterms used in their broadest sense. Particular implementations of thecompositions described in this document may also comprise an additive(e.g. one of a solubilizer, an enzyme inhibiting agent, ananticoagulant, an antifoaming agent, an antioxidant, a coloring agent, acoolant, a cryoprotectant, a hydrogen bonding agent, a flavoring agent,a plasticizer, a preservative, a sweetener, a thickener, andcombinations thereof) and/or a carrier (e.g. one of an excipient, alubricant, a binder, a disintegrator, a diluent, an extender, a solvent,a suspending agent, a dissolution aid, an isotonization agent, abuffering agent, a soothing agent, an amphipathic lipid delivery system,and combinations thereof). These additives may be solids or liquids, andthe type of additive may be generally chosen based on the type ofadministration being used. Those of ordinary skill in the art will beable to readily select suitable pharmaceutically effective additivesfrom the disclosure in this document. In particular implementations,pharmaceutically acceptable additives may include, by non-limitingexample, calcium phosphate, cellulose, stearic acid, croscarmelosecellulose, magnesium stearate, and silicon dioxide.

As used in this document, “pharmaceutically effective” is a phrase usedin its broadest sense, including, by non-limiting example, effective ina clinical trial, for a specific patient, or only placebo-effective.

As used in this document, “Pharmaceutically acceptable” is a phrase usedin its broadest sense and may describe ingredients of a pharmaceuticalcomposition that meet Food and Drug Administration (FDA) standards,United States Pharmacopeial Standards (USP), US Department ofAgriculture (USDA) standards for food-grade materials, commonly acceptedstandards of the nutritional supplement industry, industry standards,botanical standards, or standards established by any individual. Thesestandards may delineate acceptable ranges of aspects of ingredients of apharmaceutical composition such as edibility, toxicity, pharmacologicaleffect, or any other aspect of a chemical, composition, or preparationused in implementations of a pharmaceutical composition.

Compounds/Components

A first implementation is a Carnitine compound of the formula:

wherein;Y is selected from the group consisting of a Nitrate and a Nitrite.

Applicants have cost-effectively synthesized Carnitine Nitrate bycombining nitric acid and Carnitine, mixing with water, and leaving tocrystallize. Further nitratization can take place, yielding CarnitineDinitrate or Carnitine Trinitrate. An alternative implementation maycomprise using Nitrous Acid (HNO₂) instead of Nitric Acid (HNO₃), thusyielding Carnitine Nitrite. Carnitine Nitrite has the same effects asCarnitine Nitrate, the only difference being that it requires one lessstep to yield Nitric Oxide (NO—). Mixed salts may also be used, such asin the non-limiting example of Carnitine Nitrate-Orotate. In addition,it will be understood that alternative implementations comprisingAcetyl-L-Carnitine and/or Propionyl-L-carnitine in combination with oneof a Nitrate and a Nitrite are likewise possible in accordance withthese disclosures.

Another implementation is a Taurine compound of the formula:

wherein;Y is selected from the group consisting of a Nitrate and a Nitrite.

Applicants have cost-effectively synthesized Taurine Nitrate bycombining nitric acid and Taurine, mixing with water, and leaving tocrystallize. Further nitratization can take place, yielding TaurineDinitrate or Taurine Trinitrate. An alternative implementation maycomprise using Nitrous Acid (HNO₂) instead of Nitric Acid (HNO₃), thusyielding Taurine Nitrite. Taurine Nitrite has the same effects asTaurine Nitrate, the only difference being that it requires one lessstep to yield Nitric Oxide (NO—). Mixed salts may also be used, such asin the non-limiting example of Taurine Nitrate-Orotate.

Compositions and/or formulations of the present invention may beadministered in any form, including one of a capsule, a cachet, a pill,a tablet, a powder, a granule, a pellet, a bead, a particle, a troche, alozenge, a pastille, a solution, an elixir, a syrup, a tincture, asuspension, an emulsion, a mouthwash, a spray, a drop, an ointment, acream, a gel, a paste, a transdermal patch, a suppository, a pessary,cream, a gel, a paste, a foam, and combinations thereof for example.Compositions and/or formulations of the present invention may alsoinclude a acceptable additive (e.g. one of a solubilizer, an enzymeinhibiting agent, an anticoagulant, an antifoaming agent, anantioxidant, a coloring agent, a coolant, a cryoprotectant, a hydrogenbonding agent, a flavoring agent, a plasticizer, a preservative, asweetener, a thickener, and combinations thereof) and/or a acceptablecarrier (e.g. one of an excipient, a lubricant, a binder, adisintegrator, a diluent, an extender, a solvent, a suspending agent, adissolution aid, an isotonization agent, a buffering agent, a soothingagent, an amphipathic lipid delivery system, and combinations thereof).

Implementations of Carnitine and Taurine Nitrate and/or NitriteCompounds may also be synthesized or created in a wide variety ofmanners, and may be made from a wide variety of materials. Those ofordinary skill in the art will readily be able to select appropriatematerials and methods to manufacture and use the compounds disclosedherein.

Dosage Forms

Implementations of Carnitine and Taurine Compounds may conveniently bepresented in unit dosage form. Unit dosage formulations may be thosecontaining a daily dose or unit, a daily sub-dose, or an appropriatefraction thereof, of the administered components as described herein.

A dosage unit may include a Carnitine and/or a Taurine Compound. Inaddition, a dosage unit may include a Carnitine and Taurine Compoundadmixed with a pharmaceutically acceptable additive(s), and/or anycombination thereof.

The dosage units may be in a form suitable for administration bystandard routes. In general, the dosage units may be administered, bynon-limiting example, by the topical (including buccal and sublingual),transdermal, oral, rectal, ophthalmic (including intravitreal orintracameral), nasal, vaginal, and/or parenteral (includingsubcutaneous, intramuscular, intravenous, intradermal, intratracheal,and epidural) routes.

For the exemplary purposes of this disclosure, oral delivery may be aparticularly advantageous delivery route for administration to humansand animals of implementations of a pharmaceutical composition,optionally formulated with appropriate pharmaceutically acceptableadditives to facilitate administration.

Manufacture

Implementations of Carnitine and Taurine Compounds may be made usingconventional or other procedures. Accordingly, although there are avariety of method implementations for producing pharmaceuticalcompositions, for the exemplary purposes of this disclosure, a methodimplementation for producing a Carnitine and Taurine Compounds maycomprise: measuring specific quantities of Carnitine and/or Taurine,Nitric or Nitrous Acid and water mixed in a specific order the measuredquantities of Carnitine and/or Taurine, Nitric or Nitrous Acid andwater, and any additional pharmaceutically acceptable additives or inertingredients, and then separating the pharmaceutical composition intodiscrete quantities for distribution and/or administration.

Measuring specific quantities of Carnitine and/or Taurine, Nitric orNitrous Acid and water, and pharmaceutically acceptable additives orinert ingredients, may involve any number of steps and implementingcomponents, and measuring specific quantities of Carnitine and/orTaurine, Nitric or Nitrous Acid and water, and pharmaceuticallyacceptable additives or inert ingredients, may be accomplished readilyfrom this disclosure. For the exemplary purposes of this disclosure,measuring specific quantities of Carnitine and/or Taurine, Nitric orNitrous Acid and water, and pharmaceutically acceptable additives orinert ingredients, may comprise using a scale, a solid or liquiddispensing apparatus, or other measurement device capable of measuringsolid mass or liquid volume to produce a desired quantity of Carnitineand/or Taurine, Nitric or Nitrous Acid and water, and pharmaceuticallyacceptable ingredient.

It should be appreciated that any of the components of particularimplementations of Carnitine and Taurine Compounds may be used assupplied commercially, or may be preprocessed by, by non-limitingexample, any of the methods and techniques of agglomeration, airsuspension chilling, air suspension drying, balling, coacervation,comminution, compression, pelletization, cryopelletization, extrusion,granulation, homogenization, inclusion Compoundation, lyophilization,melting, mixed, molding, pan coating, solvent dehydration, sonication,spheronization, spray chilling, spray congealing, spray drying, or otherprocesses known in the art depending in part on the dosage form desired.The various components may also be pre-coated or encapsulated as knownin the art. It will also be clear to one of ordinary skill in the artthat appropriate additives may also be introduced to the composition orduring the processes to facilitate the preparation of the dosage forms,depending on the need of the individual process.

Mixing the measured quantities of Carnitine and/or Taurine, Nitric orNitrous Acid and water, and pharmaceutically acceptable additives orinert ingredients, may involve any number of steps and implementingcomponents, and may be accomplished readily from this disclosure. Forthe exemplary purposes of this disclosure, mixed the measured quantitiesof Carnitine and/or Taurine, Nitric or Nitrous Acid and water, andpharmaceutically acceptable additives or inert ingredients, may comprisecombining the measured quantities of Carnitine and/or Taurine, Nitric orNitrous Acid and water, and pharmaceutically acceptable additives orinert ingredients, under the influence of physical, ultrasonic, orelectrostatic forces to create a desired degree of intermingling and/orchemical reaction of the Carnitine and/or Taurine, Nitric or NitrousAcid and water and any pharmaceutically acceptable ingredients. Themixed may be accomplished when the Carnitine and/or Taurine, Nitric orNitrous Acid and water and/or any pharmaceutically acceptableingredients are in a solid, liquid, or semisolid state.

Separating Carnitine and Taurine Compounds into discrete quantities fordistribution may involve any number of steps and implementingcomponents, and separating t Carnitine and Taurine Compounds intodiscrete quantities for distribution may be accomplished readily fromthis disclosure. For the exemplary purposes of this disclosure,separating the Amino Acid Compound into discrete quantities fordistribution may involve utilizing a specific piece of equipment, forexample, a conventional tablet forming apparatus to shape the formedcomposition into individual tablets, each containing a desired dose ofCarnitine and Taurine Compounds. The separating process may beaccomplished when the Carnitine and Taurine Compounds are in a solid,liquid, or semisolid state.

Those of ordinary skill in the art will be able to readily selectmanufacturing equipment and pharmaceutically acceptable additives orinert ingredients to manufacture implementations of Carnitine andTaurine Compounds. For the exemplary purposes of this disclosure, someexamples of pharmaceutically acceptable additives or inert ingredientsand manufacturing process are included below, particularly those thatrelate to manufacture of implementations of Carnitine and TaurineCompounds in tablet form. Notwithstanding the specific examples given,it will be understood that those of ordinary skill in the art willreadily appreciate how to manufacture implementations of Carnitine andTaurine Compounds according to the other methods of administration anddelivery disclosed in this document.

A particular implementation of Carnitine and Taurine Compounds mayinclude a lubricant. Lubricants are any anti-sticking agents, glidants,flow promoters, and the like materials that perform a number offunctions in tablet manufacture, for example, such as improving the rateof flow of the tablet granulation, preventing adhesion of the tabletmaterial to the surface of the dies and punches, reducing interparticlefriction, and facilitating the ejection of the tablets from the diecavity. Lubricants may comprise, for example, magnesium stearate,calcium stearate, talc, and colloidal silica.

Particular implementations of Carnitine and Taurine Compounds may alsoinclude a binder. Binders are any agents used to impart cohesivequalities to powdered material through particle-particle bonding.Binders may include, for example, matrix binders (e.g. dry starch, drysugars), film binders (e.g. celluloses, bentonite, sucrose), andchemical binders (e.g. polymeric cellulose derivatives, such as methylcellulose, carboxy methyl cellulose, and hydroxy propyl cellulose); andother sugar, gelatin, non-cellulosic binders and the like.

Disintegrators may be used in particular implementations of Carnitineand Taurine Compounds to facilitate the breakup or disintegration oftablets after administration. Disintegrators may include, for example,starch, starch derivatives, clays (e.g. bentonite), algins, gums (e.g.guar gum), cellulose, cellulose derivatives (e.g. methyl cellulose,carboxymethyl cellulose), croscarmellose sodium, croscarmellosecellulose, and other organic and inorganic materials.

Implementations of Carnitine and Taurine Compounds may include diluents,or any inert substances added to increase the bulk of the Carnitine andTaurine Compounds to make a tablet a practical size for compression.Diluents may include, for example, calcium phosphate, calcium sulfate,lactose, mannitol, magnesium stearate, potassium chloride, and citricacid, among other organic and inorganic materials.

Buffering agents may be included in Carnitine and Taurine Compounds andmay be any one of an acid and a base, where the acid is, for example,propionic acid, p-toluenesulfonic acid, salicylic acid, stearic acid,succinic acid, tannic acid, tartaric acid, thioglycolic acid, ortoluenesulfonic acid, and the base is, for example, ammonium hydroxide,potassium hydroxide, sodium hydroxide, sodium hydrogen carbonate,aluminum hydroxide, calcium carbonate, and other organic and inorganicchemicals.

Implementations of Carnitine and Taurine Compounds may also beadministered through use of amphipathic lipid delivery systems (such asliposomes and unilamellar vesicles), caplet systems, oral liquidsystems, parenteral and/or intravenous systems, topical systems (creams,gels, transdermal patches, etc.), intranasal systems, rectal or vaginalsystems, and many other delivery methods and/or systems known to thoseof ordinary skill in the art. Those of ordinary skill in the art willreadily be able to select additional pharmaceutically acceptableadditives to enable delivery of implementations of a pharmaceuticalcomposition from the disclosure in this document.

With respect to delivery of particular implementations of Carnitine andTaurine Compounds, for the exemplary purposes of this disclosure,tablets may be utilized. Tablets are any solid pharmaceutical dosageform containing a pharmaceutically acceptable active agent or agents tobe administered with or without suitable pharmaceutically acceptableadditives and prepared either by compression or molding methods wellknown in the art. Tablets have been in widespread use and remain popularas a dosage form because of the advantages afforded both to themanufacturer (e.g., simplicity and economy of preparation, stability,and convenience in packaging, shipping, and dispensing) and the patient(e.g., accuracy of dosage, compactness, portability, blandness of taste,and ease of administration). Although tablets are most frequentlydiscoid in shape, they may also be round, oval, oblong, cylindrical,rectangular or triangular, for example. The tablets may be optionallyscored so that they may be separated into different dosages. They maydiffer greatly in size and weight depending on the amount of thepharmaceutically acceptable active agent or agents present and theintended route of administration. They are divided into two generalclasses, (1) compressed tablets, and (2) molded tablets.

Tablets and other orally discrete dosage forms, such as capsules,cachets, pills, granules, pellets, beads, and particles, for example,may optionally be coated with one or more enteric coatings, sealcoatings, film coatings, barrier coatings, compress coatings, fastdisintegrating coatings, or enzyme degradable coatings for example.Multiple coatings may be applied for desired performance. Further,dosage forms may be designed for, by non-limiting example, immediaterelease, pulsatile release, controlled release, extended release,delayed release, targeted release, synchronized release, or targeteddelayed release. For release/absorption control, carriers may be made ofvarious component types and levels or thicknesses of coats. Such diversecarriers may be blended in a dosage form to achieve a desiredperformance. In addition, the dosage form release profile may beeffected by a polymeric matrix composition, a coated matrix composition,a multi-particulate composition, a coated multiparticulate composition,an ion-exchange resin-based composition, an osmosis-based composition,or a biodegradable polymeric composition.

While manufacture of implementations of Carnitine and Taurine Compoundshave been described in particular sequences of steps and/or inparticular forms, it will be understood that such manufacture is notlimited to the specific order of steps or forms as disclosed. Any stepsor sequences of steps of manufacture of implementations of Carnitine andTaurine Compounds in any form are given as examples of possible steps orsequences of steps or potential forms and not as limitations, since manypossible manufacturing processes and sequences of steps may be used tomanufacture Carnitine and Taurine Compound implementations in a widevariety of forms.

Use

Implementations of Carnitine and Taurine Compounds are particularlyuseful in increasing vasodilation and blood flow in humans and animals.However, implementations are not limited to uses relating tovasodilation modification, and the like. Rather, any descriptionrelating to the foregoing is for the exemplary purposes of thisdisclosure. It will be understood that implementations of Carnitine andTaurine Compounds may encompass a variety of uses and are not limited intheir uses. For example, possible uses may be, by non-limiting example,improved athletic performance, increased distribution to muscles, fasteraction than single-administration Carnitine and/or Taurine, enhancedwater solubility, prevention of Nitrate tolerance, and/or counteringNitric Oxide inhibiting effects of certain Amino Acids.

In conventional preparations of Nitrate compounds, “tolerance,” aparticular side effect, has been observed in many patients. This isunfortunate because the effectiveness of Nitrate on vasodilation is welldocumented. “Tolerance” occurs when a subject's reaction to Nitratedecreases so that larger doses are required to achieve the same effect.A Mar. 3, 2000 report in the British Journal of Pharmacology indicatesthat “tolerance to the dilator effects of nitrates remains a persistingtherapeutic problem.” Raymond J. MacAllister “Arginine and NitrateTolerance” available athttp://www.nature.com/bjp/journal/v130/n2/full/0703340a.html, thecontents of which are hereby incorporated herein by reference.

Empirical studies indicate that Nitrates are useful for theirvasolidating effects. Common Nitrates include nitroglycerin andisosorbide dinitrate. Nitrates exert their vasodilating effect throughtheir reduction to Nitrites. In vivo, Nitrates are reduced to Nitritesand, in the blood vessels' epithelial cells, Nitrite reacts with a thioldonor (mainly glutathione) to yield Nitric Oxide. Louis J. Ignarro,“After 130 years, the Molecular Mechanism of Action of Nitroglycerin isRevealed” (Jun. 11, 2002) available athttp://www.pnas.org/cgi/content/full/99/12/7816?ck=nck, the contents ofwhich are hereby incorporated herein by reference.

The Nitric Oxide inhibiting characteristics of the Amino Acid Glutaminehave been well documented in a number of studies. In particular, a Mar.28, 2006 report in the American Journal of Physiology has found thatGlutamine inhibits Nitric Oxide production by downregulation of eNOSsynthase. Masao Kakoki, et al. “Amino acids as Modulators ofEndothelium-Derived Nitric Oxide.” available athttp://ajprenal.physiology.org/cgi/content/full/291/2/F297, the contentsof which are hereby incorporated by reference.

A January 2006 Journal of Nutrition report indicates that the Amino AcidLeucine promotes anabolism and stimulates muscle protein synthesis.Michael J. Rennie, et al. “Branched-Chain Amino Acids as Fuels andAnabolic Signals in Human Muscle” available athttp://jn.nutrition.org/cgi/content/full/136/1/264S, the contents ofwhich are hereby incorporated by reference.

Empirical studies indicate that the Amino Acid Norvaline inhibits theenzyme arginase and thus decreases the rate of conversion of the AminoAcid Arginine to urea. Takeyori Saheki, et al. “Regulation of UreaSynthesis in Rat Liver” available athttp://jb.oxfordjournals.org/cgi/content/abstract/86/3/745?ijkey=5d134456b7443ca36c809269462276e532549798&keytype2=tf_ipsecsha,the contents of which are hereby incorporated by reference.

An October 2004 Journal of Nutrition report indicates that the AminoAcid Ornithine promotes anabolism and stimulates muscle proteinsynthesis. Michael J. Rennie, et al. “Branched-Chain Amino Acids asFuels and Anabolic Signals in Human Muscle” available athttp://jn.nutrition.org/cgi/content/full/136/1/264S, the contents ofwhich are hereby incorporated by reference.

Empirical studies indicate that the Amino Acids Beta-Beta Alanine andL-Histidine support carnosine production. M. Dunnett, “Influence of OralBeta-Beta Alanine and L-Histidine Supplementation on the CarnosineContent of the Gluteus Medius” Equine Veterinary Journal Supplement,available athttp://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=10659307&ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed,the contents of which are hereby incorporated by reference.

Empirical studies further indicate that the Amino Acids Beta Alanine andL-Histidine increase muscle power, recuperation and stamina.ii YoshihiroSuzuki “High Level of Skeletal Muscle Carnosine Contributes to theLatter Half of Exercise Performance During 30-S Maximal Cycle ErgometerSprinting” in the Japanese Journal of Physiology, available athttp://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=12139778&ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum,the contents of which are hereby incorporated by reference.

Accordingly, Applicants have discovered that the Carnitine compoundaccording to the first implementation, when ingested, provides enhancedNitric Oxide (NO—) production while providing improved vasodilationeffects over single administration of Carnitine, the singleadministration of Nitrates, or the single administration of Nitrites.Improved vasodilation may, in turn, provide better circulation anddistribution of Carnitine in the body. Absorption may be improved sinceAmino Acid derivative salts with inorganic acids may be much more watersoluble than single administration Amino Acid derivatives. Applicantshave also discovered that the vasodilating effect of Carnitine Nitrateand Taurine Nitrate manifests as fast as any nitrate, since the NO₃—group of the salt requires minimal conversion to yield Nitric Oxide.Likewise, the development of tolerance to the nitrate component of themolecule may be prevented with the presence of Carnitine and/or Taurine.

1. A Carnitine Compound consisting essentially of a nitrate or nitriteof Carnitine.
 2. A Taurine Compound consisting essentially of a nitrateor nitrite of Taurine.
 3. A method for increasing water solubility ofone of Carnitine and Taurine in a human or animal, which comprisesadministering a pharmaceutically effective amount of one of a CarnitineCompound consisting essentially of a nitrate or nitrite of Carnitine anda Taurine Compound consisting essentially of a nitrate or nitrite ofTaurine to the human or animal.
 4. The method of claim 3, whereinincreasing water solubility further comprises increasing thebioabsorption of one of Carnitine and Taurine in a human or animal. 5.The method of claim 3, wherein increasing water solubility furthercomprises increasing the vasodilative characteristics of one ofCarnitine and Taurine in a human or animal.
 6. A method for treating thedevelopment of nitrate tolerances in a human or animal, which comprisesadministering a pharmaceutically effective amount of one of a CarnitineCompound consisting essentially of a nitrate or nitrite of Carnitine anda Taurine Compound consisting essentially of a nitrate or nitrite ofTaurine to the human or animal.